The biologic significance of changes in uterine luminal proteins was investigated. Protein fractions did not stimulate 8-celled rabbit embryos, but permitted morulae to develop in vitro. Blastocysts which developed blastocoeles either in vitro or in vivo showed immediate radial expansion when placed in medium supplemented with nonfractionated uterine proteins; whereas, those cultured in bovine serum albumin supplemented medium tended to "hatch" and the blastocyst coverings did not thin or expand. This study demonstrates that synchrony between the embryo and the uterine environment is necessary to permit normal embryonic development.